肿瘤微环境中免疫细胞在口腔鳞状细胞癌发生发展中作用的研究进展  

Research progress on the role of immune cells in the tumor microenvironment in the development and progression of oral squamous cell carcinoma

作　　者：廖新月 冯燕 余丽 LIAO Xinyue;FENG Yan;YU Li(Department of Pediatric Dentistry,The Affiliated Stomatology Hospital,Southwest Medical University,Luzhou 646000,China;School of Sto-matology,Southwest Medical University,Luzhou 646000,China;Luzhou Key Laboratory of Oral&Maxillofacial Re-construction and Regeneration,Southwest Medical University,Luzhou 646000,China;Department of Periodontal Mu-cosal Disease,The Affiliated Stomatology Hospital,Southwest Medical University,Luzhou 646000,China)

机构地区：[1]西南医科大学附属口腔医院儿童口腔科,四川泸州646000 [2]西南医科大学口腔医学院,四川泸州646000 [3]西南医科大学口颌面修复重建和再生泸州市重点实验室,四川泸州646000 [4]西南医科大学附属口腔医院牙周黏膜病科,四川泸州646000

出　　处：《口腔疾病防治》2025年第2期160-168,共9页Journal of Prevention and Treatment for Stomatological Diseases

基　　金：四川省科技厅重点研发项目(2022YFS0634);四川省医学青年创新课题计划(Q23028)。

摘　　要：口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)是头颈部最常见的恶性肿瘤,其强侵袭性、高淋巴结转移的特点是患者预后差的主要原因。肿瘤微环境(tumor microenvironment,TME)是肿瘤细胞生存的特殊微环境。肿瘤相关免疫细胞(tumor-associated immune cell,TAIC)是TME主要的基质细胞。一方面,TAIC调控与OSCC相关的增殖、侵袭、上皮-间充质转化(epithelial mesenchymal transformation,EMT)和抗肿瘤免疫。肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)中的促肿瘤型M2-TAMs通过MIF/NLRP3/IL-1β分子轴促进OSCC的侵袭转移;肿瘤相关中性粒细胞(tumor-associated neutrophils,TANs)中的促肿瘤型N2-TANs通过JAK2/STAT3通路促进OSCC细胞的增殖和EMT;髓源性抑制细胞(myeloid-derived suppressor cells,MDSCs)分泌白细胞介素(interleukin,IL)-6、IL-10和转化生长因子(transforming growth factor,TGF)-β促进OSCC进展;而T淋巴细胞可分泌IL-17促进炎症进展,也可分泌IL-10和TGF-β抑制炎症介导的肿瘤免疫反应;自然杀伤(natural killer,NK)细胞识别并攻击肿瘤细胞进而抑制OSCC的进展。另一方面,TAIC之间的相互作用也调控OSCC的进展。M2-TAMs分泌IL-10和程序性死亡配体(programmed death-ligand,PD-L)-1促进T淋巴细胞的凋亡调控OSCC的侵袭转移;N2-TANs分泌血凝素样氧化低密度脂蛋白受体-1和精氨酸酶-1抑制T淋巴细胞的增殖和细胞毒性;MDSCs通过抑制程序性细胞死亡受体(programmed cell death,PD)-1/PD-L1信号传导抑制CD8+T淋巴细胞的增殖和抗肿瘤效应;同时,MDSCs也可降低CD3-zeta链的表达和干扰素-γ(interferon-γ,IFN-γ)的分泌抑制T淋巴细胞增殖;而肿瘤浸润淋巴细胞(tumor-infiltrating lymphocytes,TILs)与NK细胞的数量在OSCC进展中呈正相关关系。因此,靶向调控OSCC中TAIC及其相关的信号通路,精准靶向TAIC之间的相互作用将有望提高免疫治疗疗效从而抑制OSCC进展。笔者对近年来TME中TAIC及其相互作用对OOral squamous cell carcinoma(OSCC),the most common type of head and neck malignancy,has a poor prognosis owing to its high invasiveness and high rate of cervical lymph node metastasis.The tumor microenvironment(TME)is a complex microenvironment that is essential for tumor cell survival.Tumor-associated immune cell(TAIC),the main stromal cell of TME,regulates the proliferation,invasion,epithelial-mesenchymal transformation(EMT),and anti-tumor immunity of OSCC.M2-tumor-associated macrophages(TAMs)promote the invasion and metastasis of OSCC through the macrophage migration inhibitory factor/NOD-like receptor family pyrin domain containing 3/interleukin(IL)-1βaxis,while N2-tumor-associated neutrophils(TANs)regulate the proliferation and EMT of OSCC through the Janus kinase 2/signal transducer and activator of transcription 3 pathway.Meanwhile,myeloid-derived suppressor cells(MDSCs)accel-erate the progression of OSCC by secreting IL-6,IL-10,and transforming growth factor(TGF)-β;T cells promote inflam-mation by secreting IL-17 and inhibit inflammation-mediated tumor immune response by secreting IL-10 and TGF-β;and natural killer(NK)cells recognize and attack OSCC cells to inhibit OSCC progression.TAIC interaction network al-so regulates OSCC progression.M2-TAMs regulate the invasion and metastasis of OSCC by promoting T cell apoptosis through the secretion of IL-10 and programmed death-ligand(PD-L)-1,while N2-TANs inhibit T cell proliferation and cytotoxicity by secreting LOX-1 and arginase-1.MDSCs inhibit the proliferation and anti-tumor effects of CD8+T cells through the inactivation of programmed cell death(PD)-1/PD-L1 signaling.Additionally,MDSCs inhibit the proliferation of T cells by decreasing the expression of the CD3-zeta chain and interferon-γ(IFN-γ).Moreover,tumor-infiltrating lym-phocytes and NK cells were found to be positively correlated in OSCC progression.Therefore,target regulation,related signaling pathways,and the interaction network of TAIC may serve as promising therapeutic targets in the immu

关 键 词：肿瘤微环境 肿瘤相关免疫细胞 肿瘤相关巨噬细胞 肿瘤相关中性粒细胞 髓源性抑制细胞 T淋巴细胞 自然杀伤细胞 口腔鳞状细胞癌 基质细胞 肿瘤免疫 

分 类 号：R78[医药卫生—口腔医学]